Familial Clinical Heterogeneity of Medullary Thyroid Cancer with Germline RET S891A Protooncogene Mutation: 7-Year Follow-up with Successful Sorafenib Treatment.

Hereditary forms of Medullary thyroid carcinoma (MTC) are rare. Different phenotypes with the same mutation may be due to differences in the timing of RET activation steps, additional mutations in other regions of the gene, or the co-occurrence of germline and somatic mutations, which is an infrequent possibility. Here, we aim to present the different features and difficulties in the follow-up of three family members with the same germline mutation. A 4-year-old male patient with respiratory distress was diagnosed with MTC and found to have a heterozygous germline mutation C.2671T>G(S891A) in the RET gene (classified as intermediate risk according to ATA). As the tumor was inoperable, treatment with a tyrosine kinase inhibitor (sorafenib) was initiated. Sorafenib has prevented tumor progression for seven years. Whole exome sequencing (WES) did not identify additional mutations. Segregation analysis showed the same mutation in the asymptomatic mother and sister. In our case, thyroid tissues were examined for somatic mutations, and SDHA c.1223C>T (p.S408L) was found. The clinical presentation of rare mutations such as RET p.S891A differed among family members carrying the same germline mutation. Our index case's more severe clinical presentation may be due to an additional somatic mutation. Sorafenib treatment can be an option for advanced MTC and may prevent disease progression.

Combined tumour of aberrant cytokeratin expressing acral lentiginous melanoma and poroma: Diagnostic challenge.

Combined tumours are uncommon and therefore these tumours may pose a diagnostic challenge. In the current case report, it is aimed to present the clinicopathological features of a combined tumour including melanoma with aberrant cytokeratin expression and poroma.

Patterns and Grading of Gastrointestinal Graft-Versus-Host Disease: A Clinicopathologic Correlation Study.

BACKGROUND: The present study investigated gastrointestinal involvement patterns of acute graft-versus-host disease and assessed the correlation of pathologic severity with clinical grading. METHODS: Pathology reports of gastrointestinal (GI) endoscopic biopsies taken from 164 post-hematopoietic stem cell transplant patients with at least 1 endoscopic gastrointestinal biopsy diagnosed as "consistent with acute graft-versus-host disease" between 2005 and 2019 were retrieved from the automated hospital database. Endoscopic, pathologic and clinical gradings were performed using Freiburg criteria, Lerner and modified Seattle-Glucksberg grading systems, respectively. RESULTS: The majority of the patients (n = 140, 85.4%) were investigated with more than one biopsy from various gastrointestinal sites with a total of 479 biopsies: 44 (9.2%) esophagus, 90 (18.8%) stomach, 91 (19.0%) duodenum, 20 (4.2%) terminal ileum, 32 (6.7%) right colon, 87 (18.2%) left colon and, 115 (23.9%) rectum. Overall, lower gastrointestinal (n = 118/126, 93.6%) and upper gastrointestinal (n = 91/97, 93.8%) involvements were similar (P = .3). While the most severely affected site was duodenum (P = .021) in upper gastrointestinal, pathologic grades were similar in lower gastrointestinal sites, though more severe than upper gastrointestinal (P = .003). Pathologic grading had a low positive correlation with both clinical (r = 0.308, P = .001) and endoscopic grading (coefficient: 0.261, P = .003). CONCLUSION: Considering the similar graft-versus-host disease frequency of upper and lower gastrointestinal tract, distal colon evaluation with rectosigmoidoscopy seems to be a practical approach in patients with suspected gastrointestinal graft-versus-host disease. As it was positively correlated with both endoscopic and clinical grade, pathologic grading should be performed in these patients to assess gastrointestinal involvement patterns.

Can Radiomics Analyses in 18F-FDG PET/CT Images of Primary Breast Carcinoma Predict Hormone Receptor Status?

OBJECTIVES: This study aimed to investigate the role of preoperative 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomics features and metabolic parameters of primary breast tumors in predicting hormone receptor (HR) positivity. METHODS: A total of 153 patients with breast carcinoma who underwent preoperative 18F-FDG PET/CT were included. All PET/CT images were retrospectively reevaluated. Radiomics features of primary breast lesions reflecting tumor heterogeneity as well as standardized uptake value (SUV) metrics (SUVmin, SUVmean, SUVmax, and SUVpeak) and volumetric parameters such as metabolic tumor volume and total lesion glycolysis (TLG) were extracted by commercial texture analysis software package (LIFEx; https://www.lifexsoft.org/ index.php). WEKA and SPSS were used for statistical analysis. Binary logistic regression analysis was used to determine texture features predicting HR positivity. Accuracy, F-measure, precision, recall, and precision-recall curve area were used as data-mining performance criteria of texture features to predict HR positivity. RESULTS: None of the radiomics parameters were significant in predicting HR status. Only SUV metrics and TLG were statistically important. Mean ± standard deviations for SUVmean, SUVmax, and SUVpeak for the HR-negative group were significantly higher than those in the HR-positive group (6.73±4.36 vs. 5.20±3.32, p=0.027; 11.55±7.42 vs. 8.63±5.23, p=0.006; and 8.37±6.81 vs. 5.72±4.86; p=0.012). Cut-off values of SUVmean, SUVmax, and SUVpeak for the prediction of HR positivity were 4.93, 8.35, and 6.02, respectively. Among data-mining methods, logistic regression showed the best performance with accuracy of 0.762. CONCLUSION: In addition to the relatively limited number of patients in this study, radiomics parameters cannot predict the HR status of primary breast cancer. SUV levels of the HR-negative group were significantly higher than those of the HR-positive group. To clarify the role of metabolic and radiomics parameters in predicting HR status in breast cancer, further studies involving a larger study population are needed.

Histopathology of non-coeliac gluten sensitivity.

Diagnosis of non-coeliac gluten sensitivity (NCGS) remains still problematic due to the subjectiveness and lack of a specific biomarker. We aimed to compare NCGS duodenal mucosae with healthy individuals and Marsh type 1 coeliac disease (CD), to determine whether NCGS has characteristic histological features. A total of 44 healthy controls, 42 NCGS, and 44 type 1 CD patients were selected according to clinical, serological, and laboratory data. Duodenal biopsies were evaluated on H&E, CD, and CD117 for villus/crypt ratio, IEL counts/100 enterocytes, uneven distribution pattern with clusters of IELs in the villous epithelium, linear distribution of T lymphocytes in the basal lamina propria, and eosinophils and mast cells in the lamina propria. IEL counts were within normal range in controls (13 ± 7.65), normal or mildly increased in NCGS (24.7 ± 10.46), and increased in CD (58.79 ± 14.97) on CD3. The presence of uneven distribution pattern of IELs in the villous epithelium was significantly higher in NCGS (90.5%), in contrast to controls (27.3%) and CD (34.1%). The presence of linear distribution of T lymphocytes in the basal lamina propria (68.2%, 76.2%, 78.1%), eosinophil counts (6.85 ± 3.42, 6.21 ± 2.8, 7.62 ± 3.89), and mast cell counts (25.1 ± 5.1, 26 ± 2.9, 30.3 ± 4.4) was similar in controls, NCGS, and CD, respectively. In conclusion, duodenal mucosae in NCGS are characterized by preserved villous architecture, normal or mildly increased IELs with clusters, and eosinophils and mast cells within normal limits. We believe uneven distribution of IELs with clusters in the villous epithelium can be used as a supportive histopathological tool for NCGS in the right clinical setting.

Subungual Glomangiomyoma.

Glomus tumors are relatively rare benign tumors originated from normal glomus bodies. These tumors make up approximately 2% of all hand tumors and are most commonly found in the nail matrix and proximal nail bed of the hands. Histopathologically, they are classified into solid glomus tumor, glomangioma, and the least common type glomangiomyoma. Here we report an unusual case of subungual glomangiomyoma of the toe with dermatoscopic and histopathologic findings.

Duodenal bulb biopsy in the diagnostic work-up of coeliac disease.

Coeliac disease (CD) is an autoimmune enteropathy which can present with patchy mucosal lesions. The aim of the present study is to investigate the significance of duodenal bulb biopsy in the diagnostic work-up of CD in both pediatric and adult patients, and to highlight the key points for pathologists. D1 (duodenal bulb) and D2 (distal duodenum) biopsies of 153 newly diagnosed serology-positive CD patients were evaluated for villous/crypt ratio and intraepithelial lymphocyte (IEL) counts on CD3-stained slides and were classified according to Marsh. Mucosal pathology was patchy in 15% (13% only D1 and 2% only D2) of patients, and 85% of patients had diffuse mucosal pathology involving both D1 and D2 biopsies which showed concordant histology in 60% and discordant in 25% of the cases. Though majority of the patients (75%) with only D1 involvement were pediatric cases, no significant difference was found between pediatric and adult patients when all cases were considered (17 vs 14%). Our results clearly indicate that without D1 sampling, diagnosis of CD would have been missed in a significant number of cases (13%), thereby highlighting the importance of taking duodenal biopsies from multiple sites in the diagnostic work-up of CD. We, therefore, conclude that every biopsy piece from both D1 and D2 should be carefully evaluated for the whole spectrum of mucosal changes caused by gluten ingestion and classified using a scheme based on Marsh to allow recognition of mild lesions.

Basosquamous carcinoma and melanoma collision tumor in a child with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis associated with hypersensitivity to ultraviolet radiation (UVR), being due to defects involving the nucleotide excision repair pathway. Patients with XP are prone to develop multiple cutaneous neoplasms including non-melanoma skin cancers and melanoma. Collision tumors in patients with XP have been reported in the literature including the following lesions, actinic keratosis, basal cell carcinoma, squamous cell carcinoma, and in situ melanoma. Herein, we present a rare collision tumor composed of melanoma and basosquamous carcinoma in a 13-year-old XP patient and describe the dermoscopic features.

Discriminant value of IEL counts and distribution pattern through the spectrum of gluten sensitivity: a simple diagnostic approach.

Intraepithelial lymphocytosis (IELosis) with or without villous abnormality is a characteristic feature of gluten sensitivity (GS) including celiac disease (CD) and non-celiac-GS, although various conditions may also be associated with IELosis. In order to distinguish GS from the other causes of IELosis, a threshold for IEL counts is necessary. We aimed to determine a cut-off value for IELs and monitor its value in the spectrum of GS in a large cohort. For this purpose, the duodenal biopsies from four groups of individuals including Types 1 (n = 88) and 3 (n = 92) CD, non-CD IELosis (n = 112), and control (n = 82) cases, all strictly defined by their clinical, laboratory, and serologic features, were evaluated. The number of IELs/100 enterocytes and their distribution pattern on H&E- and CD3-immunostained sections were assessed for each group. Kruskal-Wallis test and ROC curve analysis for discriminant value were employed for statistics. The IEL counts showed an increasing trend through the spectrum of mucosal pathology including controls (12.06; 21.40), non-CD IELosis (28.62; 39.46), Type 1 CD (49.27; 60.15), and Type 3 CD (58.53; 71.74) both on H&E- and CD3-immunostained sections, respectively (p < 0.001). ROC analysis revealed 20.5 on H&E and 28.5 on CD3 as the IEL cut-off values with a sensitivity of 95.9 and 87.7% and a specificity of 98.8% and 93.9%, respectively, for controls. IELs showed a diffuse distribution pattern per biopsy piece and per villus (90.9%, 100%, respectively) in nearly all of Type 1 CD cases (p < 0.001). An IEL cut-off value of 20.5 on H&E together with a diffuse distribution pattern seem to be the most discriminant features for the diagnosis of CD, even for the milder forms of the disease.

Classification chaos in coeliac disease: Does it really matter?

The spectrum of mucosal pathology in coeliac disease (CD), initially defined by Marsh in 1992 has been subjected to several modifications in the following years by Oberhuber, then by Corazza and Villanaci, and finally by Ensari. The present study, aimed to end the ongoing confusion regarding the classification of mucosal pathology in CD by applying all the classifications proposed so far on a large series of cases. A total of 270 duodenal biopsies taken from the distal duodenum of patients with a diagnosis of CD were included in the study. All biopsies were classified according to Marsh, Oberhuber, Corazza Villanaci, and Ensari classification schemes. For statistical analyses cases were divided into three groups: Group 1 included type 1 lesions in Marsh, Ensari, and Oberhuber and grade A in Corazza Villanaci classifications. Group 2 comprised of type 2 lesions in Marsh and Ensari classifications together with type2, type 3a and 3b lesions in Oberhuber classification and grade B1 lesions in Corazza Villanaci classification. Group 3 included type 3 lesions in Marsh and Ensari classifications, and type 3c lesions in Oberhuber, and grade B2 lesions in Corazza Villanaci classifications. The kappa value was 1.00 (excellent) for group 1, 0.53 (fair) for group 2 and 0.78 (excellent) for group 3 (p<0.0001). These results suggest that any of the above classification system would serve similar purposes in the diagnosis of CD. Therefore, it is advisable that the pathologist should use the simplest reliable scheme.

An Unusual Manifestation of Renal Angiomyolipoma: Pulmonary Fat Embolism.

Renal angiomyolipoma (AML) is the most common benign renal mesenchymal tumors. AMLs are usually asymptomatic and frequently affect women. Only epithelioid variant has malignant potential. Although life-threatening complications related to retroperitoneal bleeding and massive hematuria are possible, it is often detected incidentally. Pulmonary embolism as the first symptom is extremely rare. Herein, we present a case of renal AML who admitted with pulmonary embolism symptoms.